Phytochemicals that modify MAPK signaling
| Phytochemical | Target Tissue/Cells | Effects | Involved Molecular Mechanism | Reference |
|---|---|---|---|---|
| EGCG | Cervical cells | Increase p53, p21(WAF-1), and p27(KIP-1) levels, reduce cyclin E level, and reduced CDK2 kinase activity | Inhibited EGFR-dependent activation of the MAPKs ERK1/ERK2 | Sah et al. (2004) |
| MCF10A cell line, MDA-MB-231 cell line | Inhibitory effect toward HGF/Met signaling | Repressed ERK phosphorylation | Bigelow and Cardelli (2006) | |
| DU145 cells | Prevent phosphorylation of tyrosine 1234/1235 | Reduced the HGF-induced phosphorylation of ERK | Duhon et al. (2010) | |
| ARO cells | Inhibit the growth of the cells | Suppressed phosphorylation of ERK1/ERK2, JNK, and p38 | Lim and Cha (2011) | |
| RLE cells | Inhibit gap junctional intercellular communication and phosphorylation of Cx43 | Phosphorylation of ERK1/ERK2 | Kang et al. (2008b) | |
| PC-3 cell | Inhibit the cell proliferation | Activation ERK1/ERK2 pathway | Albrecht et al. (2008) | |
| NHBE cells | Downregulation of NF-κB-regulated proteins cyclin D1 | Inhibited phosphorylation of ERK1/ERK2, JNK, and p38 MAPKs | Syed et al. (2007) | |
| HT-29, HCA-7 cell line | Inhibit NF-κB, decreased COX-2 promoter activity | Downregulated the ERK1/ERK2 | Peng et al. (2006) | |
| DU145, LNCaP cells | Decrease the levels of PI3K and p-Akt | Increase ERK1/ERK2 | Siddiqui et al. (2004) | |
| Polyphenon E, caffeine | Female A/J mice | Inhibit cell proliferation | Lowered levels of c-Jun and Erk 1/Erk2 phosphorylation | Lu et al. (2006) |
| 6-ME) | HUVECs | Inhibit angiogenesis and suppress tumor growth | Inhibited VEGF-induced phosphorylation of ERK1/ERK2 MAPK | Bellou et al. (2012) |
| Resveratrol | EBV-positive BL cells | Arrest cell cycle progression in G(1) phase | Induction of p38 MAPK phosphorylation and suppression of ERK1/ERK2 signaling pathway | De Leo et al. (2011) |
| MCF-7 cells | Lead to apoptosis | Inhibited activation of ERK1/ERK2 | Lin et al. (2006) | |
| A375 cell line | Inhibit growth and induce apoptosis | Induced phosphorylation of ERK1/ERK2 | Niles et al. (2003) | |
| THP-1 cells | Inhibit LPS-induced IL-8 production | inhibited ERK and p38 MAPK phosphorylation | Oh et al. (2009) | |
| Curcumin | Hepatic stellate cells | Abrogate the membrane translocation of GLUT2 and suppress GLUT2 expression | Interrupting the p38 MAPK signaling pathway abrogate the membrane translocation | Lin and Chen (2011) |
| B16 cells (melanoma) | Inhibit melanin synthesis and cellular tyrosinase activity | Activation of ERK and p38 MAPK | Tu et al. (2012) | |
| 3T3-L1 cells | Restore nuclear translocation of β-catenin | Inhibited ERK, JNK, and p38 | Ahn et al. (2010) | |
| Chalcones | A549 cells | Induce cytotoxicity and inhibit NF-κB | Activation of ERK1/ERK2 and JNK | Warmka et al. (2012) |
| Sappanchalcone | Oral cancer cells | Suppress the cells growth and induce apoptosis | Activation of p38, ERK, and JNK | Lee et al. (2011b) |
| Butein (3,4,2′,4′-tetrahydroxychalcone) | MDA-MB-231 cells | Inhibit the proliferation of breast cancer cell and promote apoptosis | Decreased the phosphorylation of ERK, increased p38 activity | Yang et al. (2012) |
| Extra virgin olive oil | HER2-gene amplified JIMT-1 cell line | Inhibit mitosis to promote G2/M cell cycle arrest | Activated the p38 MAPK | Oliveras-Ferraros et al. (2011) |
| Fisetin | HeLa cells | Reduce tumor growth and induce apoptosis | Activation of the phosphorylation of ERK1/ERK2 | Ying et al. (2012) |
| Genistein | Caco-2 cells | Increase Nrf2 mRNA and protein expression | Activated the ERK1/ERK2 | Zhai et al. (2013) |
| Grape seed procyanidin | A2780/T cells | Inhibit P-gp expression | Inhibited MAPK/ERK pathway | Zhao et al. (2013a) |
| Hydroxytyrosol | Human colon adenocarcinoma cells | Block cell cycle G2/M | Strong inhibition of ERK1/ERK2 | Corona et al. (2009) |
| Kaempferol | U-2 OS cells | Inhibit metastasis of cells | Attenuated the MAPK signaling pathway | Chen et al. (2013) |
| Myricetin | T24 cells | Lead to G2/M cell cycle arrest and induce apoptosis | Phosphorylation of p38 MAPK | Sun et al. (2012) |
| Red ginseng essential oil | HepG2 cells | Diminish oxidative stress and restore the activity and expression of SOD, catalase, GPx | Inhibited the phosphorylation of upstream MAPKs | Bak et al. (2012a) |
| Hesperetin | Postmitotic neuron cells | Partially reverse staurosporine-induced cell death | Increases in the level of ERK1/ERK2 phosphorylation | Rainey-Smith et al. (2008) |
| Cortical neurons | Prevent neuronal apoptosis | Activation of both Akt and ERK1/ERK2 | Vauzour et al. (2007) | |
| l-Theanine | SH-SY5Y cells | Attenuate both rotenone- and dieldrin-induced DNA fragmentation and apoptotic death | Rotenone- and dieldrin-induced downregulation of ERK1/ERK2 phosphorylation | Cho et al. (2008) |
| Resveratrol | Rat primary astroglia | Increase BDNF and GDNF production | Induced the phosphorylation of ERK1/ERK2 | Zhang et al. (2012a) |
| Oroxylin A | Rat cortical neurons | Increase BDNF production | Activated ERK1/ERK2 MAPK | Jeon et al. (2011) |
| Honokiol | Rat cortical neurons | Neurite outgrowth | ERK1/ERK2 activation | Zhai et al. (2005) |
| Curcumin | Neural progenitor cells | Promote cell proliferation and adult hippocampal neurogenesis | Activated ERK and p38 kinases | Kim et al. (2008) |
| Heptamethoxyflavone | Transient global ischemia mouse | Increase BDNF and neurogenesis | Induced the phosphorylation of ERK1/ERK2 | Okuyama et al. (2012) |
| Calycopterin | PC12 cells | Inhibit H2O2-induced nuclear translocation of NF-κB | Suppressed ERK, JNK, and p38 MAPK phosphorylation | Farimani et al. (2011) |
| Koshu (grape seed extract) | Neonatal mouse hippocampal neurons | Neuroprotective effects against excitotoxicity | Inactivation of ERK1/ERK2 | Narita et al. (2011) |
| Mollugin | Mouse hippocampal HT22 cell line, BV2 cells | Increase expression of HO1, activate HO | Activated the p38 MAPK pathway | Jeong et al. (2011) |
| EGCG | HT-29 cells | Induce apoptotic cell death | Inhibition of JNK pathway | Chen et al. (2003) |
| Human chondrosarcoma cells | Induce apoptosis | Induced p38 and JNK phosphorylation | Yang et al. (2011b) | |
| Isoorientin | HepG2 cells | Induce mitochondria-mediated apoptosis | Suppressed ERK1/ERK2, and activation of JNK and p38 MAPK | Yuan et al. (2013) |
| Luteolin | Neuro-2a mouse neuroblastoma cells | Induce apoptosis through ER stress and mitochondrial dysfunction | Activation of JNK, p38, and ERK | Choi et al. (2011) |
| Curcumin, tricostatin A | Breast cancer cells | Decrease cell viability | Increased phosphorylated JNK and phosphorylated p38 | Yan et al. (2013) |
| Resveratrol | JB6 mouse epidermal cell line | Induce p53 activation and induce apoptosis | Activated JNKs | She et al. (2002) |
| Quercetin | HepG2 cells | Induce cell death | Activation of the JNK pathway | Granado-Serrano et al. (2010) |
| Baicalein | HT22 cells | Reduce endoplasmic reticulum stress–induced apoptosis | Modulated the endoplasmic reticulum stress-mediated activation of p38 MAPK and JNK pathways | Choi et al. (2010) |
| Luteolin | Rat cortical neurons | Neuroprotective effect | Protective mechanism is mediated by preventing of p38 MAPK and JNK pathways and caspase-3 activations | Cheng et al. (2010) |
| Oxyresveratrol | SH-SY5Y cells | Neuroprotective effects against PD | Attenuated 6-OHDA–induced phosphorylation of JNK and c-Jun | Chao et al. (2008) |
| Curcumin | PD mouse model | Improve behavioral deficits and prevent dopaminergic neuronal death | Inhibited MPTP/MPP(+)-induced phosphorylation of JNK1/JNK2 | Yu et al. (2010b) |
| Apigenin | BV-2 cell line | Inhibit the production of NO and prostaglandin E2 | Suppressed p38 MAPK, JNK phosphorylation | Ha et al. (2008) |
6-ME, 6-methoxyequol; CDK, cyclin-dependent kinase; EBV, Epstein–Barr virus; EGFR, epidermal growth factor receptor; GLUT, glucose transporter; HGF, hepatocyte growth factor; P-gp, P-glycoprotein.